A de novo missense mutation in ZMYND11 is associated with global developmental delay, seizures, and hypotonia

Abstract

Recently, mutations in the zinc finger MYND-type containing 11 (ZMYND11) gene were identified in patients with autism spectrum disorders, intellectual disability, aggression, and complex neuropsychiatric features, supporting that this gene is implicated in 10p15.3 microdeletion syndrome. We report a novel de novo variant in the ZMYND11 gene (p.Ser421Asn) in a patient with a complex neurodevelopmental phenotype. The patient is a 24-yr-old Caucasian/Filipino female with seizures, global developmental delay, sensorineural hearing loss, hypotonia, dysmorphic features, and other features including a happy disposition and ataxic gait similar to Angelman syndrome. In addition, this patient had uncommon features including eosinophilic esophagitis and multiple, severe allergies not described in similar ZMYND11 cases. This new case further supports the association of ZMYND11 with autistic-like phenotypes and suggests that ZMYND11 should be included in the list of potentially causative candidate genes in cases with complex neurodevelopmental phenotypes.

Keywords: absence seizures; absent speech; asthma; atonic seizures; broad-based gait; central hypoxia; clinodactyly of the 5th finger; congenital sensorineural hearing impairment; esophagitis; gait ataxia; gastroesophageal reflux; microcephaly; neurogenic bladder; prominent epicanthal folds; seasonal allergy; severe global developmental delay.

Figure 1.

Patient phenotypic assessment depicting: (A) facial dysmorphism, (B) clinodactyly of the fifth finger, (C) small feet (7.7 in), and (D) epicanthal folds.

Figure 2.

Magnetic resonance imaging (MRI) images indicate that the ventricles and cerebral sulci are moderately prominent for the patient's age and show abnormal myelination with peripheral myelination less than expected. The radiology report impression concludes cerebral atrophy and delayed myelination without evidence of focal abnormality.

Figure 3.

(A) High conservation of the ZMYND11 region across multiple species. (B) Reported variants of ZMYND11. The variant described in this report is in red.